Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

Abstract

The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.

Factors influencing scar formation following Bacille Calmette-Guérin (BCG) vaccination

“…The higher likelihood of BCG scarring in participants with prior BCG vaccination history may relate to an underlying immunological boosting phenomenon, as BCG revaccination has been associated with more pronounced local injection site reactions [ 34 ], larger scar size [ 35 ] and enhanced protective effects (against respiratory tract infections) in studies in adolescents [ 36 ] and adults [ 37 ]. BCG injection site reactions (presence and size) have been shown to correlate with the magnitude of the mycobacteria-specific T-cell immune responses [ 10 ] as well as specific and heterologous cytokine responses [ 9 ] in vitro .…”

Revamping the BCG revaccination strategy: Records to recall, or just call it phoenix?

“… 12 , 17 To consider BCG revaccination, we must acknowledge that the rate of adverse events (AE) also varies globally. While BCG vaccine batch variability was found by Soh and colleagues (2014) to affect the occurrence of AEs, 18 Villanueva et al 19 did not find any association between the BCG vaccine batch and AEs. There is thus a paucity of evidence comparing the effectiveness and safety of different BCG batches.…”

“… 3 This finding is recalled in this issue (see below). Villanueva et al 19 reported an increased risk of injection site abscess and lymphadenopathy following BCG revaccination in Australian health care workers (HCW) during the influenza vaccination campaign.…”

The safety of co-administration of Bacille Calmette-Guérin (BCG) and influenza vaccines

“…Questions addressed the presence, time to onset, duration, and severity of pain, erythema, swelling and tenderness at the vaccination site. Information on BCG vaccination site reaction was collected in a similar way, and has been published elsewhere [ 16 ].…”